Genetic Variation in the Nuclear and Organellar Genomes Modulates Stochastic Variation in the Metabolome, Growth, and Defense – “Systems biology is largely based on the principal that the link between genotype and phenotype is deterministic, and, if we know enough, can be predicted with high accuracy. In contrast, recent work studying transcription within single celled organisms has shown that the genotype to phenotype link is stochastic, i.e. a single genotype actually makes a range of phenotypes even in a single environment. Further, natural variation within genes can lead to each allele displaying a different phenotypic distribution. To test if multi-cellular organisms also display natural genetic variation in the stochastic link between genotype and phenotype, we measured the metabolome, growth and defense metabolism within an Arabidopsis RIL population and mapped quantitative trait loci. We show that genetic variation in the nuclear and organeller genomes influence the stochastic variation in all measured traits. Further, each trait class has distinct genetics underlying the stochastic variance, showing that there are different mechanisms controlling the stochastic genotype to phenotype link for each trait.” – h/t kevin mitchell! who tweeted: “Some genomes are ‘noisier’ than others – robustness of developmental outcome is itself a genetic trait.“

Evolutionary pattern in the OXT-OXTR system in primates: Coevolution and positive selection footprints – “It was previously believed that placental mammals present no variability in oxytocin (OXT). The present study reports novel data on the diversity of OXT and its receptor (OXTR) in primate species, including New World monkeys. Contrary to prior expectations, we found three novel OXT forms and several OXTR nonsynonymous changes not previously described. In the Cebidae family, signals of positive selection were found for an OXT variant at position 8, which is associated with larger litter sizes. We detected positive selection for OXTR forms and report a coevolutionary process between changes in OXT and OXTR.”

Effects of the demographic transition on the genetic variances and covariances of human life history traits – “The recent demographic transitions to lower mortality and fertility rates in most human societies have led to changes and even quick reversals in phenotypic selection pressures. This can only result in evolutionary change if the affected traits are heritable, but changes in environmental conditions may also lead to subsequent changes in the genetic variance and covariance (the G matrix) of traits. It currently remains unclear if there have been concomitant changes in the G matrix of life history traits following the demographic transition. Using 300 years of genealogical data from Finland, we found that four key life history traits were heritable both before and after the demographic transition. The estimated heritabilities allow a quantifiable genetic response to selection during both time periods, thus facilitating continued evolutionary change. Further, the G matrices remained largely stable but revealed a trend for an increased additive genetic variance and thus evolutionary potential of the population after the transition.” – h/t ruben c. arslan!

Mapping granny: ancestry inference for admixed individuals – “In the December issue of G3: Genes|Genomes|Genetics, Yang et al. describe a method for ancestry inference of admixed individuals that uses a geographic approach to explicitly model some of the messy realities of populations. Testing the new method on data from the Population Reference Sample project, the authors were able to localize the grandparents of admixed Europeans to within around 500 kilometres of their reported ancestry, while simultaneously identifying which segments of each person’s genome were inherited from each ancestor.”

Different neurodevelopmental symptoms have a common genetic etiology – “Parents of all Swedish 9- and 12-year-old twin pairs born between 1992 and 2002 were targeted for interview regarding problems typical of autism spectrum disorders, ADHD and other neurodevelopmental conditions (response rate: 80 percent). Structural equation modeling was conducted on 6,595 pairs to examine the genetic and environmental structure of 53 neurodevelopmental problems. One general genetic factor accounted for a large proportion of the phenotypic covariation among the 53 symptoms. Three specific genetic subfactors identified ‘impulsivity,’ ‘learning problems,’ and ‘tics and autism,’ respectively.” – h/t jayman! who tweeted: “More evidence for the p-factor. Common genetic factor underlies many mental disorders in study of all Swedish twins.”

Mendelian and polygenic inheritance of intelligence: A common set of causal genes? Using next-generation sequencing to examine the effects of 168 intellectual disability genes on normal-range intelligence – “Despite twin and family studies having demonstrated a substantial heritability of individual differences in intelligence, no genetic variants have been robustly associated with normal-range intelligence to date. This is largely ascribed to the high polygenicity of intelligence, i.e., to its being subject to the effects of a large number of genes of individually small effect. Intellectual disability, on the other hand, frequently involves large effects of single genetic mutations, many of which have been identified…. Using an existing pool of known intellectual disability genes, we constructed a set of 168 candidate genes for normal-range intelligence, and tested their association with intelligence in 191 individuals (aged 5–18) sampled from the high and low ends of the IQ distribution. In particular, we 1) employed exon sequencing to examine the possible effects of rare genetic variants in the 168 genes, and 2) used polygenic prediction to examine the overall effect of common genetic variants in the candidate gene set in a larger sample (N = 2125, mean age 20.4, SD = 14.1). No significant association between the candidate gene set and intelligence was detected.”

Educated parents more important than rich parents – “Having a mobile phone, a video recorder and a game computer are associated with lower scholastic ability, and the only substantial positive correlation is with the number of books, and of course the cause may not be the books themselves, but the intellect and character of the families who choose to buy books.” – from dr. james thompson.

French lesson – “Modern France is founded on Western principles of equality, human betterment, and universal morality. Anyone anywhere can become French. That view, the official one, seems more and more disconnected from reality.” – from peter frost.

Insights into hominin phenotypic and dietary evolution from ancient DNA sequence data – “Nuclear genome sequence data from Neandertals, Denisovans, and archaic anatomically modern humans can be used to complement our understanding of hominin evolutionary biology and ecology through i) direct inference of archaic hominin phenotypes, ii) indirect inference of those phenotypes by identifying the effects of previously-introgressed alleles still present among modern humans, or iii) determining the evolutionary timing of relevant hominin-specific genetic changes. Here we review and reanalyze published Neandertal and Denisovan genome sequence data to illustrate an example of the third approach.”

Skip Your Annual Physical – “Regardless of which screenings and tests were administered, studies of annual health exams dating from 1963 to 1999 show that the annual physicals did not reduce mortality overall or for specific causes of death from cancer or heart disease…. [S]creening healthy people who have no complaints is a pretty ineffective way to improve people’s health. If you screen thousands of people, maybe you’ll find tens whose exams suggest they might have a disease. And then upon further tests, you’ll find it is really only a few individuals who truly have something. And of those individuals, maybe one or two actually gain a health benefit from an early diagnosis. The others may have discovered a disease, but one that either would never have become clinically evident and dangerous, or one that is already too advanced to treat effectively. For instance, early detection of most thyroid cancers leads to surgery, but in many cases those cancers would not have caused serious problems, much less death. Conversely, for individuals whose annual exams lead to the diagnosis of esophageal or pancreatic cancer, the early diagnosis might extend the time they know they have cancer but is unlikely to extend their lives.” – h/t jason collins!

Variation in cancer risk among tissues can be explained by the number of stem cell divisions – “Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue’s homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to ‘bad luck,’ that is, random mutations arising during DNA replication in normal, noncancerous stem cells.”

The Strange Inevitability of Evolution – “Good solutions to biology’s problems are astonishingly plentiful…. [T]wo crucial things about the RNA sequence space. First, there are many, many possible sequences that will all serve the same function. If evolution is ‘searching’ for that function by natural selection, it has an awful lot of viable solutions to choose from. Second, the space, while unthinkably vast and multi-dimensional, is navigable: You can change the genotype neutrally, without losing the all-important phenotype. So this is why the RNAs are evolvable at all: not because evolution has the time to sift through the impossibly large number of variations to find the ones that work, but because there are so many that do work, and they’re connected to one another.” – h/t billare!

Mathematicians refute oft-cited ‘diversity trumps ability’ study – “‘Diverse groups of people bring to organizations more and different ways of seeing a problem and, thus, faster/better ways of solving it,’ Page told The New York Times in 2008. ‘The reason: the diverse groups got stuck less often than the smart individuals, who tended to think similarly,’ Page said. ‘What the model showed was that diverse groups of problem solvers outperformed the groups of the best individuals at solving problems.’ But Thompson’s paper in the Notices of the American Mathematical Society systematically dismantles Page’s sophistic mathematics.”

bonus: Deep bacteria may evolve even without passing genes on – “Bacteria living hundreds of metres below the seafloor carry more genetic changes than their peers nearer the surface – even though the deep microbes are unlikely to reproduce and undergo natural selection in its traditional sense…. The results show – for the first time, Briggs thinks – that the bacterial genomes change with depth: the micro-organisms at 554 metres carry more mutations in genes that code for energy-related processes like cell division and biosynthesis of amino acids than are seen in their shallower counterparts…. [I]f you take evolution in its broader sense to mean genetic changes across the population, then it might be occurring even without cell division, says Briggs. That’s because in theory, bacteria in these environments grow so slowly that they may survive for hundreds of thousands of years. Individual bacteria might have begun life at the seafloor before being gradually buried, over a period of thousands of years, as more sediment accumulated at the bottom of the sea. If so, perhaps the bacteria now at 554 metres were rare cells in the initial population that have now come to dominate because the other cells, which didn’t carry their genetic mutations, have all died.”

bonus bonus: Insights into the evolution of longevity from the bowhead whale genome – “The bowhead whale (Balaena mysticetus) is estimated to live over 200 years and is possibly the longest-living mammal. These animals should possess protective molecular adaptations relevant to age-related diseases, particularly cancer. Here, we report the sequencing and comparative analysis of the bowhead whale genome and two transcriptomes from different populations. Our analysis identifies genes under positive selection and bowhead-specific mutations in genes linked to cancer and aging. In addition, we identify gene gain and loss involving genes associated with DNA repair, cell-cycle regulation, cancer, and aging. Our results expand our understanding of the evolution of mammalian longevity and suggest possible players involved in adaptive genetic changes conferring cancer resistance. We also found potentially relevant changes in genes related to additional processes, including thermoregulation, sensory perception, dietary adaptations, and immune response.”